Titanium dioxide (E 171) is no longer considered safe, according to the updated ESFA evaluation. Rigorous methodology and new data helped fill in data gaps and conclude that genotoxicity concerns cannot be ruled out.
EFSA has updated its safety assessment of the food additive titanium dioxide (E 171), following a request by the European Commission. The assessment took into consideration many thousands of studies that have become available since EFSA’s previous assessment in 2016, including new scientific evidence and data on nanoparticles.
Prof. Maged Younes, Chair of EFSA’s expert Panel on Food Additives and Flavorings (FAF), said in a statement: “Taking into account all available scientific studies and data, the Panel concluded that titanium dioxide can no longer be considered safe as a food additive. A critical element in reaching this conclusion is that we could not exclude genotoxicity concerns after the consumption of titanium dioxide particles. After oral ingestion, the absorption of titanium dioxide particles is low; however, they can accumulate in the body”.
Genotoxicity refers to the ability of a chemical substance to damage DNA, the genetic material of cells. As genotoxicity may lead to carcinogenic effects, it is essential to assess the potential genotoxic effect of a substance to conclude on its safety. Prof. Matthew Wright, both a member of the FAF Panel and chair of EFSA’s working group on E 171, said: “Although the evidence for general toxic effects was not conclusive, based on the new data and strengthened methods, we could not rule out a concern for genotoxicity and consequently we could not establish a safe level for daily intake of the food additive.” An Acceptable Daily Intake (ADI) cannot be established for E171.
In the framework of EFSA new risk assessment on E171, new knowledge on the characterization of the food additive E171 and updated guidance for the Risk Assessment of materials containing a fraction of nanoparticles has led to the broadening of the toxicological database, including a significant amount of new evidence from studies obtained with TiO2 nanoparticles.
It is important to note that in EFSA’s food additives assessments, genotoxicity is considered a standalone toxicity endpoint. Data from TiO2 genotoxicity testing provide information about potential irreversible DNA damage that may result in heritable or degenerative diseases. The available data on genotoxicity have excluded the potential for TiO2 to cause gene mutations but could not rule out concerns for other adverse effects on the genetic material of the cells.
Titanium dioxide (E 171) is authorized as a food additive in the EU according to Annex II of Regulation (EC) No 1333/2008. Risk managers at the European Commission and in the EU Member States have been informed of EFSA’s conclusions and will consider appropriate action to take to ensure consumers’ protection.
Although the majority of the genotoxic effects were reported with TiO2 nanoparticles, they were also noted with TiO2 particles greater than 100nm. Therefore, the data on genotoxicity do not allow EFSA’s experts to set a clear threshold with respect to genotoxic effects and the size of the particles that cause these effects. Different modes of action could be responsible for the genotoxic effects according to the available data. However, the data do not allow EFSA to identify a dose below which these effects do not occur. This is what leads to EFSA’s conclusion that it is unable to exclude concerns around the genotoxicity of TiO2 nanoparticles.
The assessment was conducted following a rigorous methodology and taking into consideration all evidence that has become available since EFSA’s previous assessment in 2016, including new scientific evidence and data on nanoparticles. Concretely, in the first instance, EFSA carried out an extensive review of the literature (nearly 12,000 publications) published between January 2015 and November 2020. After a first screening, EFSA identified around 200 in vivo studies and 300 in vitro studies as potentially relevant for this evaluation.
TiO2 is a particulate material, meaning that it is composed of particles of different sizes. TiO2 used as E 171 contains at most 50% of particles in the nano range (i.e. less than 100 nanometers) to which consumers may be exposed. The characterization of E171 was evaluated by EFSA’s FAF Panel in its opinion from 2019. According to data received from food business operators, the Panel noted in that opinion that there are different types of E171 on the market containing different amounts of nanoparticles. Generally speaking, the percentage of nanoparticles can vary from 5 to < 50% depending on the type of E171. For this reason, in the safety assessment of E171, our scientific experts applied the principles specified in the 2018 EFSA Scientific Committee Guidance on Nanotechnology.
Based on the available data, EFSA determines the level below which the intake of the food additive can be considered safe – the so-called Acceptable Daily Intake (ADI). At the same time, EFSA also estimates, based on the occurrence data (reported uses and use levels and analytical data), whether this ADI can be exceeded. In case the ADI will not be exceeded, the use of the food additive is considered safe.
When there are insufficient data for establishing an ADI, a margin of safety may be calculated to determine whether estimated exposure might be of potential concern. In specific cases, there is no need to set an ADI, e.g. for substances that are identical to a component that is a normal constituent in the body.
Read the full article, in Baking + Biscuit International, Issue 4 – 2021.